title: Advances towards the design and development of personalized non-small-cell lung cancer drug therapy.
abstract: BACKGROUND
  Non-small-cell lung cancer (NSCLC) subtypes are driven by specific genetic aberrations. For reasons such as this, there is a call for treatment personalization. The ability to instigate NSCLC fragmentation poses new methodological problems, and new 'driver' molecular aberrations are being discovered at an unprecedented pace.
  
  
  METHODS
  This article describes the clinical development of epidermal growth factor-tyrosine kinase inhibitors (EGFR-TKIs) and crizotinib for EGFR-mutant and anaplastic lymphoma kinase (ALK)-rearranged NSCLC. Further, the authors briefly describe the emerging molecular targets in NSCLC, in terms of both rationale for therapeutic targeting and strategies, for clinical development.
  
  
  CONCLUSIONS
  Target identification and validation in NSCLC still requires considerable effort, as not all of the molecular alterations are clear 'drivers' nor can they be efficiently targeted with available drugs. However, 50% of the NSCLC cases are without clear-defined molecular aberrations. Clinical trial methodology will need to develop novel paradigms for targeted drug development, aiming at the validation of an ideal 'biology-to-trial' approach. Despite significant challenges, a truly 'personalized' approach to NSCLC therapy appears to be within our reach.
authors.affiliation: Regina Elena National Cancer Institute, Division of Medical Oncology A , Via Elio Chianesi 53, 00144, Rome , Italy +39 06 52666919 ; +39 06 52665637 ; michelemilella@hotmail.com ; milella@ifo.it.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Vari
authors.forename: Sara
authors.initials: S
authors.lastname: Pilotto
authors.forename: Marcello
authors.initials: M
authors.lastname: Maugeri-Saccà
authors.forename: Ludovica
authors.initials: L
authors.lastname: Ciuffreda
authors.forename: Ursula
authors.initials: U
authors.lastname: Cesta Incani
authors.forename: Italia
authors.initials: I
authors.lastname: Falcone
authors.forename: Anais
authors.initials: A
authors.lastname: Del Curatolo
authors.forename: Anna
authors.initials: A
authors.lastname: Ceribelli
authors.forename: Alain
authors.initials: A
authors.lastname: Gelibter
authors.forename: Ruggero
authors.initials: R
authors.lastname: De Maria
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tortora
authors.forename: Francesco
authors.initials: F
authors.lastname: Cognetti
authors.forename: Emilio
authors.initials: E
authors.lastname: Bria
authors.forename: Michele
authors.initials: M
authors.lastname: Milella
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D058990:Molecular Targeted Therapy / Q000379:methods*; D057285:Precision Medicine / Q000379:methods*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004815:Epidermal Growth Factor; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases